Thanks to cutting-edge clinical trials at UW-Madison, transplant patients are returning to healthy lives without anti-rejection drugs.
Shawn Wiederhoeft is a pretty normal guy in his 30s. Madison Native works as a video game developer and maintains an active lifestyle. He is healthy, spends time with friends and family in the best form of his life and regularly in Southern Wisconsin.
However, it was not necessarily the case that Wiederhoeft could fully participate in life. In fact, “Uncle Shaun,” known to his family, is healthy today thanks to the new kidneys he received in 2020 from Meagan Hahn of Wauwatosa.
The transplanted kidney has a new leasing of life to Wiederhoeft and he and his sister chose to take part in cutting-edge clinical trials at the University of Wisconsin School of Medicine and Public Health, so he can also live without the need for anti-rejection drugs.
With no daily medication and only occasional health checks, Wiederhoeft says he almost forgets that he is a kidney transplant recipient.
“We have to consciously remember that there is a third kidney here,” he says. “I feel healthier than ever.”
Wiederhoeft's incredible journey from serious illness to drug-free recovery is just one of the successful international kidney transplant cases reported by an international team of physicians and researchers in the July issue of the US Transplant Journal.
UW -Dixon Kaufman, who leads the UW Health Losplant Center, led by Dr. Dixon Kaufman, professor of surgery for Madison, shared the results of a Phase 3 clinical trial assessing the efficacy and safety of a live kidney transplant resistance protocol, which also includes the transplantation of specific stem cells into temptation remis of kidney donors.
These stem cells are injected into recipients a few days after implantation, reside in the bone marrow, where they divide and proliferate into immune cells that share the genes of the organs they have donated. The goal is to prevent the recipient's immune system from attacking new organs. This would otherwise be perceived as a threat.
“This procedure does not replace the immune system, but it complements that about 5-10% of the immune system comes from donors,” Kaufmann says.
In doing so, this new method significantly suppresses the recipient's immune system and removes the need for costly rejection drugs that emphasize lifelong side effects.
The prospect of participating in clinical trials that communicated such possibilities was surreal for some of the first participants in the study, including Wiederhoeft and Hahn.
“It felt straight from science fiction novels,” says Weederhof.
The sense of entering unknown territory was even more pronounced for Prattville's sisters Barb Okey and Brenda Kuare, who were the first participants in the trial.
“To say I'm nervous – that's an understatement,” says Okey, who was injected with her stem cells in 2018 following one of Quale's kidneys. As expected, within months of the procedure, the test showed that Quale's cells circulated in Okey's blood and eventually dismissed with her anti-religious therapy. Today, the only medication Okey takes is to help control her blood pressure.
“It's amazing,” Okey says. “It's pretty amazing to have the opportunity to continue living with a new kidney and continue living without taking medication.”
Okey and Wiederhoeft are one of a small group of kidney recipients who can abandon anti-rejection drugs thanks to UW-Madison clinical trials, but there are plans to expand eligibility for this procedure.
In the early stages, we requested that the donor and recipient be siblings and be “complete” or identical matches. Kaufman says that the success of the initial trial means that eligibility can be extended to recipients of non-identical matched living donor implants, and ultimately deceased donor organs.
Kaufman described the positive outcome of the trial as “very satisfying” and as evidence of the value of a long-term investment in research.
In fact, before procedures were attempted in human patients, researchers from the Wisconsin National Center for Primate Research and elsewhere spent years testing the safety and efficacy of non-human primates. In 2023, a team led by Kaufman reported promising results from the latest primate studies that could open up a way to expand the procedure to non-identical implant pairs.
The research that made this clinical trial possible has received great support for many years from the National Institutes of Health (NIH). Kaufman acknowledges UW-Madison's track record of conducting complex biomedical research for sustainable federal investment.
“UW's clinical and research environment is outstanding,” he says. “It's a unique way to make the ability to go to other programs, train in other programs, be a faculty member in other programs, and do complex clinical trials that are successful at the University of Wisconsin, is a strong collaborative culture and a great resource. We have a tradition of moving the field forward in innovative ways to get a lot of benefits.
While awareness and support from the NIH and other funding agencies have underpinned the success of the trial, Kaufman says it is patients and donors who are willing to take part in new, potentially risky trials that are responsible for helping them progress on the ground in the end.
“Get” [the patients] This is truly what it is to go back to the path to living a happy, fulfilling life,” he says.
For Hahn, who was forced and grateful to join the trial as a Wiederhoeft donor, the outcome was immeasurably positive.
“I have to remember that Uncle Shawn is there for all the family events, and that it is his healthiest version, his most ordinary version, so I have to remember that this all happened and that this is not normal for so many people. But it's a pretty blessing for us.” ■
Dixon Kaufman, MD, PhD, Ray D. Owen is a professor at the Ministry of UW -Madison Surgery.
Research that supported this clinical trial first occurred over 12 years in non-human primates before human trials, with over $20 million in funding from the National Institutes of Health over that period (U01AI102456, MSN150727, T32AI25231, U54). The NIH also supports Wisconsin National Center for Primate Research (P51OD011106). The Phase 3 clinical trial described here was sponsored by Medeor Therapeutics (MDR-101) in connection with Stanford University.
